Background The Idiopathic Inflammatory Myopathies (IIM) is a group of rare systemic inflammatory diseases characterized by severe organ involvement and premature mortality. Several myositis specific auto-antibodies (MSAs) have been recognized and associated with specific clinical manifestations and prognosis, still many patients are autoantibody negative. Identification of new autoimmune targets will be helpful in improving diagnosis, better stratifying into subgroups, prediction of prognosis, tailoring treatment and to understand underlying biological pathways.
Objectives To identify new autoimmune targets in IIM by antigen bead array (1).
Methods A bead array with 354 antigens was used to explore the autoimmune reactivity in 881 plasma samples from patients with IIM (N=225), Systemic Lupus Erythematosus (SLE) (N=350) and population controls (N=306). The antigens were selected from initial screenings of 160 SLE-samples on a total of 5760 antigens on planar arrays, and a first verification bead array with 355 antigens. The IIM samples represented three groups of patients with distinct diagnoses: Dermatomyositis (DM, N=83), Polymyositis (PM, N=111) and Inclusion Body Myositis (IBM, N=31), who were regularly followed at the Rheumatology Unit of the Karolinska University Hospital from January 2003 until March 2014. Based on 2 possible levels of cutoff, each sample was classified as reactive to each single antigen (Ag) at low or high cut off or non-reactive.
Results In general, depending on the cutoff stringency, 86–88% of the 354 selected antigens showed reactivity in at least one sample with no difference between IIM, SLE and controls. Comparing PM, DM, IBM according to the number of samples which showed reactivity towards each single Ag, reactivity at high cut off towards NADH dehydrogenase 1 α subcomplex 11 (NDUFA11), poly(A) RNA polymerase D4 (PAPD4), CD163, l(3)mbt-like 1 (L3MBTL1) and calcium release-activated calcium modulator 2 (ORAI2) was discovered with higher frequencies in the IBM samples compared to PM and DM. In the group of IIM patients testing negative for all the known MSAs increased reactivity at high cut off was observed towards E3 ubiquitin protein ligase 2 (SIAH2), leiomodin 2 (LMO2) and RAD23 homolog A (RAD23A). In the group of IIM patients with history of malignancy and no evidence for anti-p155/140 antibodies the antigens early B-cell factor 2 (EBF2), POU class 6 homebox 1 (POUF61) and growth differentiation factor 7 (GDF7) revealed high serum reactivity. In IIM patients with interstitial lung disease increased reactivity at high cut off was found towards zinc finger protein 688 (ZNF688) and prostaglandin D2 receptor (PTGDR). A high frequency of known target reactivities (MSAs) was also confirmed.
Conclusions Reactivity towards autoantigens corresponding to human proteins was present in plasma samples from IIM, controls, and SLE. Potentially new autoimmune targets have been discovered in IIM subgroups, although further validation in independent cohorts is needed.
Ayoglu B1 et al. Anoctamin 2 identified as an autoimmune target in multiple sclerosis. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2188–93.
Disclosure of Interest None declared